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Emerging Topics in Metal Complexes: Pharmacological Activity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 13022

Special Issue Editors


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Guest Editor
1. Faculdade de Ciências e Tecnologia (FCT), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal
2. CCMAR, Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal
Interests: metals in molecular sciences; decavanadate biochemistry; polyoxometalate (POM) interactions with proteins; metals and biomedical applications
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Special Issue Information

Dear Colleagues,

Due to their pharmacological potential, metal complexes and compounds have been arousing the interest of many research centers worldwide. The structure and properties of many metal coordination compounds make them therapeutically effective. They are used not only in the treatment of some modern-age diseases but also in clinical diagnostics. Currently, metal complexes and compounds (such as polyoxometalates) are prominent players in medicine and medicinal chemistry.

The results of certain studies have demonstrated that gold (Au), silver (Ag), platinum (Pt), copper (Cu), zinc (Zn), and ruthenium (Ru) coordination compounds exhibit anti-tumor, anti-microbial, and immunosuppressive activity. Some of them, i.e., Cu and Zn complexes, have also been studied in the context of neurodegenerative illnesses such as Alzheimer’s disease, which is a constantly growing social concern. Numerous studies have also revealed the potential therapeutic benefits of vanadium (V) complexes and compounds, which are at the forefront among the different metals examined for their potential therapeutic use. Its multidirectional biological properties (i.e., antiviral, antibacterial, antiproliferative, anti-inflammatory, antihypertensive, anti-allergic, anti-oxidative, anticancer, antidiabetic, anti-ulcer, and anti-obesity activity), as well as its neuroprotective, nephroprotective, and cardioprotective effects, provide a basis for studies of the unique class of pharmacological agents containing this metal.

Despite the progress in the knowledge of the pharmacological activity of certain metals and their complexes, further studies are still needed, as the mechanisms of action of the potential drugs containing metal ions are not sufficiently recognized yet. Moreover, the side effects of the use of metal coordination compounds in the treatment of some diseases (mainly cancer) and resistance to treatment are a serious problem in modern medicine. Therefore, there is a constant search for new therapeutics based on metal complexes that would ensure better treatment results and contribute to a significant slowdown in the progression of the disease. The therapeutic targets, bioavailability, and pharmacokinetics of metal-containing compounds have to be clarified in detail with reference to metal-based drugs, which may guarantee potential clinical success.

We invite authors to submit original research papers or review articles on the pharmacological activity of metal coordination compounds with a focus on strategies improving their pharmacological features and on links between metal-containing complexes and potential therapies of human pathologies with mechanistic analysis.

Potential topics include, but are not limited to:

  • Current strategies for the synthesis of metal complexes and/or compounds with biological properties;
  • Methods of improvement of existing metal-based drugs in order to enhance their therapeutic potential;
  • Biological and pharmacological effects of new metal-containing complexes and/or compounds (in vitro/in vivo studies);
  • Metal coordination compounds in modern cancer therapy and in new strategies for the treatment of neurodegenerative diseases;
  • Metal ligands in the biological activity of complexes;
  • Mechanisms of action of metal-containing compounds;
  • Pharmacokinetics and pharmacodynamics of metal complexes;
  • Metal coordination compounds in laboratory diagnostics and clinical trials.

Dr. Agnieszka Ścibior
Prof. Dr. Juan Llopis
Prof. Dr. Manuel Aureliano
Guest Editors

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Keywords

  • metal complexes
  • polyoxometalates
  • biological activity
  • pharmacokinetic parameters
  • mechanistic analysis
  • cancer/neurodegenerative diseases
  • innovative strategies
  • laboratory diagnostics
  • clinical studies

Published Papers (10 papers)

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Editorial

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6 pages, 1426 KiB  
Editorial
Emerging Topics in Metal Complexes: Pharmacological Activity
by Agnieszka Ścibior, Manuel Aureliano and Juan Llopis
Int. J. Mol. Sci. 2024, 25(9), 4982; https://doi.org/10.3390/ijms25094982 - 3 May 2024
Viewed by 527
Abstract
This Special Issue (SI), ”Emerging Topics in Metal Complexes: Pharmacological Activity”, includes reports updating our knowledge on metals with multidirectional biological properties and metal-containing compounds/complexes for their potential therapeutic applications, with a focus on strategies improving their pharmacological features [...] Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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Research

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13 pages, 1506 KiB  
Article
Zinc(II) Iminopyridine Complexes as Antibacterial Agents: A Structure-to-Activity Study
by Silvia de la Mata Moratilla, Sandra Casado Angulo, Natalia Gómez-Casanova, José Luis Copa-Patiño, Irene Heredero-Bermejo, Francisco Javier de la Mata and Sandra García-Gallego
Int. J. Mol. Sci. 2024, 25(7), 4011; https://doi.org/10.3390/ijms25074011 - 4 Apr 2024
Viewed by 713
Abstract
Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and [...] Read more.
Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate. The antibacterial effect of the Zn(II) complexes was studied against planktonic bacterial cells of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains. The results showed a moderate biocide activity in both types of planktonic bacteria, which arises from the metal complexation to the Schiff base ligand. Importantly, we confirmed the crucial effect of the metal, with Zn(II) improving the activity of Cu(II) counterparts previously reported. On the other hand, the impact of the inorganic ligands was not significant for the antibacterial effect but was relevant for the complex solubility. Finally, as proof of concept of topical antibacterial formulation, we formulated an emulsion containing the most lipophilic Zn(II) complex and confirmed a sustained release for 24 h in a vertical cell diffusion assay. The promising activity of iminopyridine Zn(II) complexes is potentially worth exploring in more detailed studies. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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22 pages, 4452 KiB  
Article
Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution
by Marko Stojanović, Mirjana B. Čolović, Jovana Lalatović, Aleksandra Milosavljević, Nada D. Savić, Kilian Declerck, Branimir Radosavljević, Mila Ćetković, Tamara Kravić-Stevović, Tatjana N. Parac-Vogt and Danijela Krstić
Int. J. Mol. Sci. 2024, 25(5), 2569; https://doi.org/10.3390/ijms25052569 - 22 Feb 2024
Viewed by 1003
Abstract
Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells–Dawson polyoxometalate, [...] Read more.
Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells–Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats’ general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD—0.67 ± 0.12; 1/5 MAD—0.59 ± 0.07; 1/10 MAD—0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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28 pages, 6041 KiB  
Article
Copper(II) Complexes with 1-(Isoquinolin-3-yl)heteroalkyl-2-ones: Synthesis, Structure and Evaluation of Anticancer, Antimicrobial and Antioxidant Potential
by Łukasz Balewski, Tomasz Plech, Izabela Korona-Głowniak, Anna Hering, Małgorzata Szczesio, Andrzej Olczak, Patrick J. Bednarski, Jakub Kokoszka and Anita Kornicka
Int. J. Mol. Sci. 2024, 25(1), 8; https://doi.org/10.3390/ijms25010008 - 19 Dec 2023
Viewed by 1179
Abstract
Four copper(II) complexes, C14, derived from 1-(isoquinolin-3-yl)heteroalkyl-2-one ligands L14 were synthesized and characterized using an elemental analysis, IR spectroscopic data as well as single crystal X-ray diffraction data for complex C1. The stability of complexes C1 [...] Read more.
Four copper(II) complexes, C14, derived from 1-(isoquinolin-3-yl)heteroalkyl-2-one ligands L14 were synthesized and characterized using an elemental analysis, IR spectroscopic data as well as single crystal X-ray diffraction data for complex C1. The stability of complexes C14 under conditions mimicking the physiological environment was estimated using UV-Vis spectrophotometry. The antiproliferative activity of both ligands L14 and copper(II) compounds C14 were evaluated using an MTT assay on four human cancer cell lines, A375 (melanoma), HepG2 (hepatoma), LS-180 (colon cancer) and T98G (glioblastoma), and a non-cancerous cell line, CCD-1059Sk (human normal skin fibroblasts). Complexes C14 showed greater potency against HepG2, LS180 and T98G cancer cell lines than etoposide (IC50 = 5.04–14.89 μg/mL vs. IC50 = 43.21–>100 μg/mL), while free ligands L14 remained inactive in all cell lines. The prominent copper(II) compound C2 appeared to be more selective towards cancer cells compared with normal cells than compounds C1, C3 and C4. The treatment of HepG2 and T98G cells with complex C2 resulted in sub-G1 and G2/M cell cycle arrest, respectively, which was accompanied by DNA degradation. Moreover, the non-cytotoxic doses of C2 synergistically enhanced the cytotoxic effects of chemotherapeutic drugs, including etoposide, 5-fluorouracil and temozolomide, in HepG2 and T98G cells. The antimicrobial activities of ligands L24 and their copper(II) complexes C24 were evaluated using different types of Gram-positive bacteria, Gram-negative bacteria and yeast species. No correlation was found between the results of the antiproliferative and antimicrobial experiments. The antioxidant activities of all compounds were determined using the DPPH and ABTS radical scavenging methods. Antiradical tests revealed that among the investigated compounds, copper(II) complex C4 possessed the strongest antioxidant properties. Finally, the ADME technique was used to determine the physicochemical and drug-likeness properties of the obtained complexes. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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17 pages, 8704 KiB  
Article
Decavanadate-Bearing Guanidine Derivatives Developed as Antimicrobial and Antitumor Species
by Andreea Dumitrescu, Catalin Maxim, Mihaela Badea, Arpad Mihai Rostas, Alexandra Ciorîță, Alina Tirsoaga and Rodica Olar
Int. J. Mol. Sci. 2023, 24(24), 17137; https://doi.org/10.3390/ijms242417137 - 5 Dec 2023
Cited by 1 | Viewed by 956
Abstract
To obtain biologically active species, a series of decavanadates (Hpbg)4[H2V10O28]·6H2O (1) (Htbg)4[H2V10O28]·6H2O; (2) (Hgnd)2(Hgnu)4[V10 [...] Read more.
To obtain biologically active species, a series of decavanadates (Hpbg)4[H2V10O28]·6H2O (1) (Htbg)4[H2V10O28]·6H2O; (2) (Hgnd)2(Hgnu)4[V10O28]; (3) (Hgnu)6[V10O28]·2H2O; and (4) (pbg = 1-phenyl biguanide, tbg = 1-(o-tolyl)biguanide, gnd = guanidine, and gnu = guanylurea) were synthesized and characterized by several spectroscopic techniques (IR, UV-Vis, and EPR) as well as by single crystal X-ray diffraction. Compound (1) crystallizes in space group P-1 while (3) and (4) adopt the same centrosymmetric space group P21/n. The unusual signal identified by EPR spectroscopy was assigned to a charge-transfer π(O)→d(V) process. Both stability in solution and reactivity towards reactive oxygen species (O2 and OH·) were screened through EPR signal modification. All compounds inhibited the development of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis bacterial strains in a planktonic state at a micromolar level, the most active being compound (3). However, the experiments conducted at a minimal inhibitory concentration (MIC) indicated that the compounds do not disrupt the biofilm produced by these bacterial strains. The cytotoxicity assayed against A375 human melanoma cells and BJ human fibroblasts by testing the viability, lactate dehydrogenase, and nitric oxide levels indicated compound (1) as the most active in tumor cells. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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17 pages, 4627 KiB  
Article
Synthesis and Biological Activity of a New Indenoisoquinoline Copper Derivative as a Topoisomerase I Inhibitor
by Caroline Molinaro, Nathalie Wambang, Sylvain Pellegrini, Natacha Henry, Marc F. Lensink, Emmanuelle Germain, Till Bousquet, Jérôme de Ruyck, Katia Cailliau, Lydie Pélinski and Alain Martoriati
Int. J. Mol. Sci. 2023, 24(19), 14590; https://doi.org/10.3390/ijms241914590 - 26 Sep 2023
Viewed by 1015
Abstract
Topoisomerases are interesting targets in cancer chemotherapy. Here, we describe the design and synthesis of a novel copper(II) indenoisoquinoline complex, WN198. The new organometallic compound exhibits a cytotoxic effect on five adenocarcinoma cell lines (MCF-7, MDA-MB-231, HeLa, HT-29, and DU-145) with the [...] Read more.
Topoisomerases are interesting targets in cancer chemotherapy. Here, we describe the design and synthesis of a novel copper(II) indenoisoquinoline complex, WN198. The new organometallic compound exhibits a cytotoxic effect on five adenocarcinoma cell lines (MCF-7, MDA-MB-231, HeLa, HT-29, and DU-145) with the lowest IC50 (0.37 ± 0.04 μM) for the triple-negative MDA-MB-231 breast cancer cell line. Below 5 µM, WN198 was ineffective on non-tumorigenic epithelial breast MCF-10A cells and Xenopus oocyte G2/M transition or embryonic development. Moreover, cancer cell lines showed autophagy markers including Beclin-1 accumulation and LC3-II formation. The DNA interaction of this new compound was evaluated and the dose-dependent topoisomerase I activity starting at 1 μM was confirmed using in vitro tests and has intercalation properties into DNA shown by melting curves and fluorescence measurements. Molecular modeling showed that the main interaction occurs with the aromatic ring but copper stabilizes the molecule before binding and so can putatively increase the potency as well. In this way, copper-derived indenoisoquinoline topoisomerase I inhibitor WN198 is a promising antitumorigenic agent for the development of future DNA-damaging treatments. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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13 pages, 3079 KiB  
Article
Exploring the Impact of Head Group Modifications on the Anticancer Activities of Fatty-Acid-like Platinum(IV) Prodrugs: A Structure–Activity Relationship Study
by Man Kshetri, Wjdan Jogadi, Suha Alqarni, Payel Datta, May Cheline, Arpit Sharma, Tyler Betters, Deonya Broyles and Yao-Rong Zheng
Int. J. Mol. Sci. 2023, 24(17), 13301; https://doi.org/10.3390/ijms241713301 - 27 Aug 2023
Viewed by 1234
Abstract
We conducted the first comprehensive investigation on the impact of head group modifications on the anticancer activities of fatty-acid-like Pt(IV) prodrugs (FALPs), which are a class of platinum-based metallodrugs that target mitochondria. We created a small library of FALPs (19 [...] Read more.
We conducted the first comprehensive investigation on the impact of head group modifications on the anticancer activities of fatty-acid-like Pt(IV) prodrugs (FALPs), which are a class of platinum-based metallodrugs that target mitochondria. We created a small library of FALPs (19) with diverse head group modifications. The outcomes of our study demonstrate that hydrophilic modifications exclusively enhance the potency of these metallodrugs, whereas hydrophobic modifications significantly decrease their cytotoxicity. To further understand this interesting structure–activity relationship, we chose two representative FALPs (compounds 2 and 7) as model compounds: one (2) with a hydrophilic polyethylene glycol (PEG) head group, and the other (7) with a hydrophobic hydrocarbon modification of the same molecular weight. Using these FALPs, we conducted a targeted investigation on the mechanism of action. Our study revealed that compound 2, with hydrophilic modifications, exhibited remarkable penetration into cancer cells and mitochondria, leading to subsequent mitochondrial and DNA damage, and effectively eradicating cancer cells. In contrast, compound 7, with hydrophobic modifications, displayed a significantly lower uptake and weaker cellular responses. The collective results present a different perspective, indicating that increased hydrophobicity may not necessarily enhance cellular uptake as is conventionally believed. These findings provide valuable new insights into the fundamental principles of developing metallodrugs. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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19 pages, 11678 KiB  
Article
UV-C Seed Surface Sterilization and Fe, Zn, Mg, Cr Biofortification of Wheat Sprouts as an Effective Strategy of Bioelement Supplementation
by Katarzyna Czarnek, Małgorzata Tatarczak-Michalewska, Piotr Dreher, Vishnu D. Rajput, Grzegorz Wójcik, Anna Gierut-Kot, Agnieszka Szopa and Eliza Blicharska
Int. J. Mol. Sci. 2023, 24(12), 10367; https://doi.org/10.3390/ijms241210367 - 20 Jun 2023
Cited by 3 | Viewed by 1872
Abstract
Metalloenzymes play an important role in the regulation of many biological functions. An effective way to prevent deficiencies of essential minerals in human diets is the biofortification of plant materials. The process of enriching crop sprouts under hydroponic conditions is the easiest and [...] Read more.
Metalloenzymes play an important role in the regulation of many biological functions. An effective way to prevent deficiencies of essential minerals in human diets is the biofortification of plant materials. The process of enriching crop sprouts under hydroponic conditions is the easiest and cheapest to conduct and control. In this study, the sprouts of the wheat (Triticum aestivum L.) varieties Arkadia and Tonacja underwent biofortification with Fe, Zn, Mg, and Cr solutions in hydroponic media at four concentrations (0, 50, 100, and 200 µg g−1) over four and seven days. Moreover, this study is the first to combine sprout biofortification with UV-C (λ = 254 nm) radiation treatment for seed surface sterilization. The results showed that UV-C radiation was effective in suppressing seed germination contamination by microorganisms. The seed germination energy was slightly affected by UV-C radiation but remained at a high level (79–95%). The influence of this non-chemical sterilization process on seeds was tested in an innovative manner using a scanning electron microscope (SEM) and EXAKT thin-section cutting. The applied sterilization process reduced neither the growth and development of sprouts nor nutrient bioassimilation. In general, wheat sprouts easily accumulate Fe, Zn, Mg, and Cr during the applied growth period. A very strong correlation between the ion concentration in the media and microelement assimilation in the plant tissues (R2 > 0.9) was detected. The results of the quantitative ion assays performed with atomic absorption spectrometry (AAS) using the flame atomization method were correlated with the morphological evaluation of sprouts in order to determine the optimum concentration of individual elements in the hydroponic solution. The best conditions were indicated for 7-day cultivation in 100 µg g−1 of solutions with Fe (218% and 322% better nutrient accumulation in comparison to the control condition) and Zn (19 and 29 times richer in zinc concentration compared to the sprouts without supplementation). The maximum plant product biofortification with magnesium did not exceed 40% in intensity compared to the control sample. The best-developed sprouts were grown in the solution with 50 µg g−1 of Cr. In contrast, the concentration of 200 µg g−1 was clearly toxic to the wheat sprouts. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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12 pages, 1529 KiB  
Article
Elucidating the Therapeutic Potential of Bis(Maltolato)OxoVanadium(IV): The Protective Role of Copper in Cellular Metabolism
by Lorenzo Rivas-García, Alfonso López-Varela, José L. Quiles, María Montes-Bayón, Pilar Aranda, Juan Llopis and Cristina Sánchez-González
Int. J. Mol. Sci. 2023, 24(11), 9367; https://doi.org/10.3390/ijms24119367 - 27 May 2023
Cited by 1 | Viewed by 1119
Abstract
Vanadium (V) is a trace mineral whose biological activity, role as a micronutrient, and pharmacotherapeutic applications remain unknown. Over the last years, interest in V has increased due to its potential use as an antidiabetic agent mediated by its ability to improve glycemic [...] Read more.
Vanadium (V) is a trace mineral whose biological activity, role as a micronutrient, and pharmacotherapeutic applications remain unknown. Over the last years, interest in V has increased due to its potential use as an antidiabetic agent mediated by its ability to improve glycemic metabolism. However, some toxicological aspects limit its potential therapeutic application. The present study aims to evaluate the effect of the co-treatment with copper (Cu) and bis(maltolato)oxovanadium(IV) (BMOV) as a possible strategy to reduce the toxicity of BMOV. Treating hepatic cells with BMOV reduced cell viability under the present conditions, but cell viability was corrected when cells were co-incubated with BMOV and Cu. Additionally, the effect of these two minerals on nuclear and mitochondrial DNA was evaluated. Co-treatment with both metals reduced the nuclear damage caused by BMOV. Moreover, treatment with these two metals simultaneously tended to reduce the ND1/ND4 deletion of the mitochondrial DNA produced with the treatment using BMOV alone. In conclusion, these results showed that combining Cu and V could effectively reduce the toxicity associated with V and enhance its potential therapeutic applications. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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Review

Jump to: Editorial, Research

35 pages, 5367 KiB  
Review
CNS-Related Effects Caused by Vanadium at Realistic Exposure Levels in Humans: A Comprehensive Overview Supplemented with Selected Animal Studies
by Agnieszka Ścibior, Juan Llopis, Paweł Piotr Dobrakowski and Tomasz Męcik-Kronenberg
Int. J. Mol. Sci. 2023, 24(10), 9004; https://doi.org/10.3390/ijms24109004 - 19 May 2023
Cited by 3 | Viewed by 2281
Abstract
Neurodegenerative disorders, which are currently incurable diseases of the nervous system, are a constantly growing social concern. They are progressive and lead to gradual degeneration and/or death of nerve cells, resulting in cognitive deterioration or impaired motor functions. New therapies that would ensure [...] Read more.
Neurodegenerative disorders, which are currently incurable diseases of the nervous system, are a constantly growing social concern. They are progressive and lead to gradual degeneration and/or death of nerve cells, resulting in cognitive deterioration or impaired motor functions. New therapies that would ensure better treatment results and contribute to a significant slowdown in the progression of neurodegenerative syndromes are constantly being sought. Vanadium (V), which is an element with a wide range of impacts on the mammalian organism, is at the forefront among the different metals studied for their potential therapeutic use. On the other hand, it is a well-known environmental and occupational pollutant and can exert adverse effects on human health. As a strong pro-oxidant, it can generate oxidative stress involved in neurodegeneration. Although the detrimental effects of vanadium on the CNS are relatively well recognized, the role of this metal in the pathophysiology of various neurological disorders, at realistic exposure levels in humans, is not yet well characterized. Hence, the main goal of this review is to summarize data on the neurological side effects/neurobehavioral alterations in humans, in relation to vanadium exposure, with the focus on the levels of this metal in biological fluids/brain tissues of subjects with some neurodegenerative syndromes. Data collected in the present review indicate that vanadium cannot be excluded as a factor playing a pivotal role in the etiopathogenesis of neurodegenerative illnesses, and point to the need for additional extensive epidemiological studies that will provide more evidence supporting the relationship between vanadium exposure and neurodegeneration in humans. Simultaneously, the reviewed data, clearly showing the environmental impact of vanadium on health, suggest that more attention should be paid to chronic diseases related to vanadium and to the assessment of the dose–response relationship. Full article
(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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